Journal of Essential Oil Research

ISSN: 1041-2905 (Print) 2163-8152 (Online) Journal homepage: https://www.tandfonline.com/loi/tjeo20

Eucalyptol (1,8-cineole): an underutilized ally in

respiratory disorders?

Derick M. Galan, Ngozi E. Ezeudu, Jasmine Garcia, Chalice A. Geronimo,

Nicholas M. Berry & Benjamin J. Malcolm

To cite this article: Derick M. Galan, Ngozi E. Ezeudu, Jasmine Garcia, Chalice A. Geronimo,
Nicholas M. Berry & Benjamin J. Malcolm (2020): Eucalyptol (1,8-cineole): an underutilized ally in
respiratory disorders?, Journal of Essential Oil Research, DOI: 10.1080/10412905.2020.1716867

To link to this article: https://doi.org/10.1080/10412905.2020.1716867

Published online: 26 Jan 2020.

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JOURNAL OF ESSENTIAL OIL RESEARCH
https://doi.org/10.1080/10412905.2020.1716867

REVIEW

Eucalyptol (1,8-cineole): an underutilized ally in respiratory disorders?

Derick M. Galana, Ngozi E. Ezeudua, Jasmine Garciaa, Chalice A. Geronimoa, Nicholas M. Berryb
and Benjamin J. Malcolm a
a
College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA; bEssential Oil Wizardry, Ashland, OR, USA

ABSTRACT ARTICLE HISTORY

Essential oil extracted from eucalyptus leaves has a long folkloric history of being used for the Received 13 May 2019
treatment of respiratory conditions. The primary terpenoid constituent in the essential oil of Accepted 6 January 2020
eucalyptus (EOE) is eucalyptol (1,8-cineole or cineole), which has been studied in both preclinical KEYWORDS
and clinical settings. Eucalyptol displays several pharmacologic activities that may provide ther- Cineole; eucalyptol;
apeutic effects in respiratory conditions such as anti-inflammatory and bronchodilatory effects. 1-cineole; eucalyptus;
Several clinical trials have been performed in persons affected with respiratory illness such as asthma; COPD
rhinosinusitis, bronchitis, asthma and chronic obstructive pulmonary disorder (COPD) with positive
results. The objectives of this review are to provide a mechanistic overview of EOE with a focus on
the primary constituent eucalyptol, summarize the pharmacology of eucalyptol in respiratory
conditions, describe clinical trial data that has been generated by studying eucalyptol in humans
for respiratory conditions, and discuss clinical and safety considerations for the use of EOE or
eucalyptol.

1. Background rheumatism, burns, or gingivitis (3). One method of

1.1. Ethnobotany and historical use
Eucalyptus is a genus of flowering trees and shrubs
containing several hundred species (1). Most euca-
lyptus species are native to Australia, although they
grow worldwide including many tropical and subtro-
pical climates (1). The leaves of eucalyptus are typi-
cally steam distilled to produce an aromatic extract,
eucalyptus oil or essential oil of eucalyptus (EOE).
Many species contain a saturated natural monoter-
pene known as eucalyptol (cineole or 1,8-cineole).
While different EOEs have a wide variety of mono-
terpenoid constituents, most produce eucalyptol as
their primary constituent, which can range from
~6% to over 80% depending on the species (2).
Eucalyptol is also found as a constituent of other
essential oils such as rosemary.
Eucalyptus leaves and their products have a long
history of folkloric use, especially by the Australian
Aborigines, for a wide variety of ailments, which could
be broadly classified as infectious and/or inflammatory
(2). For example, eucalyptus has been used for infec-
tions or symptoms of infection such as fever, bacterial
dysentery, pertussis (whooping cough), pulmonary
tuberculosis, cough, and other bacterial or viral respira-
tory conditions. Eucalyptus has also been used for
inflammatory illness and wound healing such as asthma,
traditional use involves placing eucalyptus leaves or
a few drops of EOE in a pot of steaming water and
covering the head with a towel, closing the eyes, and
inhaling the steamed vapor deeply for 5–10 min a few
times a day. While more research is needed to clarify if
EOE has a potential therapeutic role in many conditions
cited in folkloric medicine, a scientific evidence base has
begun to accumulate, elucidate and confirm the poten-
tial therapeutic utility of EOE for inflammatory respira-
tory conditions. For example, in Germany, EOE
products are authorized for ‘well-established use indica-
tions,’ such as chronic catarrh of the upper respiratory
tract and common cold symptoms of the upper respira-
tory tract with persisting mucus (Cold Capsules™ and
Soledum™) (4). EOE is also seen in flavored, cosmetic, or
antitussive products such as bath additives,
mouthwashes, insect repellants, ointments/balms and
cough lozenges (3,4).
The objectives of this review are to provide
a mechanistic overview of EOE with a focus on
the primary constituent eucalyptol, summarize the
pharmacology of eucalyptol in respiratory condi-
tions, describe clinical trial data that has been gen-
erated by studying eucalyptol in humans for
respiratory conditions, and discuss clinical and
safety considerations for the use of EOE or
eucalyptol.

CONTACT Benjamin J. Malcolm bmalcolm@westernu.edu

© 2020 Informa UK Limited, trading as Taylor & Francis Group
2 D. M. GALAN ET AL.
1.2. Pre-clinical studies on the mechanism essential
oil of eucalyptus in respiratory disease
Several studies in preclinical models of respiratory dis-
ease have been conducted to shed light on the potential
mechanism(s) of eucalyptol in the treatment of inflam-
matory or infectious respiratory illness (for pre-clinical
reviews see references (5,6)).
An experiment in lipopolysaccharide (LPS) sti-
mulated monocytes using eucalyptol at
a concentration of 1.5 μg/ml found significant
decreases in production of the pro-inflammatory
cytokines tumor necrosis factor-alpha (TNF-α) and
interleukin-1-beta (IL-1b) ranging from 65 to 92%
(7). Analysis of ex-vivo human monocytes after
subjects were pretreated with eucalyptol 200 mg
three times daily for 3 days by mouth has found
a~30–60% inhibition of several cytokines and
inflammatory factors including TNF-α, IL-1b, leu-
kotriene B4 (LTB4) and thromboxane B2 (8,9).
A study in human cell lines using LPS as an
inflammatory stimulant demonstrated a 0.6 mg/μL
eucalyptol extract was able to reduce inflammation
via suppression of the inflammatory gene promoter
NF-κB p65 compared with a control group (p <
0.01) (10). Recently, eucalyptol pretreatment was
shown to be able to downregulate pattern recogni-
tion receptors involved in LPS signaling, leading to
decreased phosphorylation of downstream tran-
scription factors NF-κB and p38 (11). It was also
demonstrated that anti-inflammatory effects of
eucalyptol could be abolished by deletion of the
gene coding for the transient receptor potential
member 8 (TRPM8) channel (12).
Eucalyptol has been shown to decrease mucus pro-
duction by ~66% in human ex-vivo monocytes model-
ing rhinosinusitis by downregulating genes associated
with mucous production, MUC2 and MUC19 (13).
Preparations of aromatic chemicals which contained
eucalyptol (as well as other aromatics) have been
found to increase mucociliary clearance and mucocili-
ary beat frequency (14,15). In guinea pig smooth muscle
from airways, eucalyptol has shown to produce
a relaxant or bronchodilatory effect (16). There have
also been experiments demonstrating antinociceptive
effects of eucalyptol and reduction of neuropathic pain
signaling (17,18).
Summarily, the data suggests that eucalyptol has anti-
inflammatory, expectorant, bronchodilator and analge-
sic effects; all of which may be of therapeutic utility in
respiratory conditions such as asthma, chronic obstruc-
tive pulmonary disorder (COPD), bronchitis, or other
conditions with cough as a symptom.
1.3. Pharmacokinetics and drug interaction
potential
Eucalyptol is absorbed quickly and can be present in the
blood after 5 min of inhalation, although it reaches its
peak plasma concentration around 18 min after inhala-
tion (19). Following oral ingestion in gastric resistant
capsules, eucalyptol is absorbed by the small intestine
and subsequently undergoes hepatic metabolism by
human cytochrome P450 enzymes (CYP3A4/5) into its
major metabolites of 2-α-hydroxy- and 3-α-hydroxy-
cineole that are then excreted in urine (5). It is also
excreted via expired air, meaning that eucalyptol is
able to reach the lungs, peripheral airways and sinuses
after oral ingestion.
In an older study of the metabolism and pharmacoki-
netics of eucalyptol in rats and humans, it was found that
aerosolized eucalyptol was capable of influencing plasma
concentrations of other drugs (20). In rats, either euca-
lyptol or placebo was aerosolized for 5-10 minutes for
four days. It was found that brain concentrations of
aminopyrine, amphetamine, zoxazolamine, and pento-
barbital were significantly decreased 2-6 hours after
drug administration compared to controls. In five healthy
human volunteers that received aerosolized eucalyptol
for 10 min for 10 consecutive days an increase in plasma
clearance of aminopyrine was observed in 4 of 5 partici-
pants. All drugs were administered 24 h after the last
aerosolization and the authors conclude that eucalyptol is
likely a hepatic cytochrome P450 (CYP) inducer even
when given via the inhalation route (20). Curiously,
a newer in vitro study of CYP inhibitory potency in
baculovirus-infected insect cells found that eucalyptol
had dose-dependent decreases in CYP 1A2, 2C8, 2C9,
2C19 and 3A4, especially with 100 and 500 μg/ml con-
centrations (21). Potential pharmacokinetic-based drug
interactions via CYP induction or inhibition warrants
further study with eucalyptol.
1.4. Safety and toxicology
Eucalyptus oil has a Generally Recognized As Safe status
(GRAS) in the United States (US) when used for its
intended purpose as a food additive or flavoring agent
(22). The short-term use (up to 6 months) of eucalyptol
at a dose of 100–200 mg three times daily appears to be
safe based on clinical research; however, ingestion of
larger doses of undiluted eucalyptus oil can be fatal
(3,7,23–25).
In mice, the LD50 has been estimated to be 3.67 and
3.75 ml/kg for two different types of EOE, while in rats
the LD50 eucalyptol has been estimated to be 2.48 g/kg
(26,27). EOE poisoning in humans has a predictable

toxidrome involving central nervous system (CNS)
depression, abnormal respiration (shallow or labored
breathing) and myosis as well as epigastric pain and
vomiting (25). Cardiovascular collapse can occur with
severe intoxication and seizure activity has been
reported rarely. There’s been a wide range in volume
of EOE that have resulted in toxicity, although one case
series in children concludes significant CNS depression
with ingestions >5 ml (25,28). Another source esti-
mated death to be likely at doses >30 ml (25,29).
Myriad sources of EOE from various species, extrac-
tion processes and sometimes imitation using only
synthetically produced terpenes add difficulty in deli-
neating reports of toxicity in the broader literature as
chemical impurities cannot be ruled out as potential
sources of reactions.
Side effects of nausea, heartburn, exanthema and diar-
rhea were reported in clinical trials (7,23,24,30,31).
However, the difference between placebo and eucalyptol
treatment groups was either not statistically significant or
not tested for significance (refer Table 1 for summary of
safety in the clinical trials). The broader literature has also
identified other rare, but possible, adverse effects including
contact allergy and skin reaction, vocal cord dysfunction,
and asthma exacerbation (eucalyptus pollen rather than
aromatic extract) (32).
In vitro studies of cytotoxicity or mutagenicity were
consistent with a hormetic response or a protective effect
at low doses and adverse effects at high doses (33). A repeat
dose (100, 500, or 1000 mg/kg × 50 days) reproductive
toxicity study in rats showed possible maternal and fetal
toxicity; however, it is not thought that amounts of euca-
lyptol found in foods pose a risk to pregnancy or nursing
mothers (34). Pregnancy and nursing were exclusionary
criteria in clinical studies.
2. Methods
A Medline and Google Scholar search was conducted
between database inception and 18 September 2018.
Search terms included (Eucalyptus oil or eucalyptol)
and (asthma or COPD). Searches were conducted inde-
pendently by two (JG and DG) of the authors and
discrepancies in articles to include were resolved by
a third author (BJM). Articles not available in English
or articles that featured non-Eucalyptus-based aromatic
blends containing additional terpenoids were excluded
(e.g. GeloMyrtol™). References identified for inclusion
using stated search terms and review articles were then
hand searched for additional manuscripts that met
inclusion criteria. Included articles were clinical trials
featuring human subjects with a respiratory condition
that had at least 10 participants.
JOURNAL OF ESSENTIAL OIL RESEARCH 3
3. Results
Five randomized double-blinded placebo-controlled
trials were identified for inclusion and all utilized euca-
lyptol as opposed to EOE as the interventional treat-
ment: one in participants with rhinosinusitis (24), one
in participants with acute bronchitis (23), two in parti-
cipants with asthma (7,30), and one in participants with
COPD (31). Table 1 provides summary characteristics
of included trials including samples studied, interven-
tion used, primary endpoints, main results and adverse
effects.
3.1. Rhinosinusitis
Rhinosinusitis, a common condition characterized by
inflammation of the sinus and nasal passages, results in
excessive secretions, congestion or nasal obstruction,
frontal headache upon bending over, and pain/pressure
in sinuses. Risk factors include allergies, asthma or
smoking. In the trial of eucalyptol by Kehrl et al.
included participants were a mean age of 30 ± 9 years
(range 18–57 years) and 56% male. Approximately 43%
reported comorbid allergies and 44% were smokers at
baseline. The mean duration of rhinosinusitis symp-
toms was ~3.5 days prior to starting treatment with
eucalyptol or placebo. At baseline, the groups were
comparable. Significant differences in symptom scores
were apparent by day 4, favoring eucalyptol, and at day 7
only 8% of the eucalyptol group failed to achieve a 50%
reduction in symptom scores from baseline compared
with 73% of participants receiving placebo. Rhinoscopic
findings using B-scan ultrasonography validated diag-
noses and findings of the study. The results remained
significant after stratification by male/female, history of
allergy/no allergies, or smoker/nonsmoker. C-reactive
protein was reduced to a greater extent in participants
receiving eucalyptol compared to placebo, although no
differences in leukocyte counts or erythrocyte sedimen-
tation rates were observed. The authors conclude that
early intervention of acute rhinosinusitis with eucalyp-
tol has the potential to effectively relieve symptoms and
reduce antibiotic prescribing which would likely
decrease antibiotic resistance, adverse effects associated
with antibiotic use and provide economic advan-
tages (24).
3.2. Bronchitis
Bronchitis is a common condition in which the bronchi
become inflamed. The cause of the illness is usually
a viral infection, yet antibiotics are commonly and
unnecessarily prescribed. In the trial by Fischer and
 4

Table 1. Summary of eucalyptol in trials of respiratory conditions.

D. M. GALAN ET AL.

Study Sample Intervention Primary endpoint Result Adverse effects

Kehrl et al. (24) Persons with acute eucalyptol 200 mg PO TID
nonpurulent with meals vs. matching
rhinosinusitis without placebo × 7 days
indication for antibiotics Concomitant use of
aged 18–70 xylometazoline 100 μg/
n = 152 spray TID used by all
participants
Fischer & Patients with confirmed eucalyptol 200 mg PO TID
Dethlefsen (23) acute bronchitis aged ½ hour before meals vs.
18–70 matching placebo × 10
n = 242 days
Juergens et al. (7) Patients with severe eucalyptol 200 mg PO TID 20
bronchial asthma on min prior to eating vs
prednisolone therapy matching placebo × 12
aged 32–75 years weeks
n = 33 Concomitant use of oral
corticosteroids, SABA,
LABA, ICS, anticholinergics
and theophylline allowed
Worth & Patients with asthma eucalyptol 200 mg PO TID
Dethlefsen (30) taking on current ½ hour before food vs
asthma medication matching placebo × 6
aged 18–65 years months
n = 247 Concomitant use of SABA,
LABA, ICS, anticholinergics
and theophylline allowed
Worth et al. (31) Smoking or former Concomitant therapy with
smoking patients with eucalyptol TID ½ hours
moderate/severe COPD before food vs matching
aged 40–80 years placebo × 6 months
n = 242 Concomitant use of SABA,
LABA, ICS, anticholinergics
and theophylline allowed
SABA = short-acting beta-agonist; LABA = long-acting beta-agonist; ICS = inhaled corticosteroid.
PO = orally; TID = three times daily; FEV = forced expiratory volume.
Decrease in symptom sum- Baseline scores were 15.6 (possible range 0–25) at baseline in Heartburn (days 5–7) and exanthema (days
score from baseline both groups 4–7) which both resolved after eucalyptol
to day 7 Δ from baseline −12.5 ± 3.6 (eucalyptol) vs. −6.5 ± 3.5 discontinuation reported (frequency not
(placebo). p < 0.0001 defined)
Decrease in Bronchitis-Sum- Baseline score was 10.0 in treatment group and 9.7 in One patient case of heartburn that was
Score at 4 and 10 days placebo determined to be related to eucalyptol
Δ from baseline was 3.55 (eucalyptol) and 2.91(control). treatment. Not statistically significant
p < 0.0383 at day 4, differences at day 10 were NS
Maximum tolerated Reduction of 3.75 mg (95% CI: 2.15–5.35) in treatment group Heartburn and gastritis side effects were
reduction in oral steroid and 0.91 mg (95% CI: 0.03–1.85 mg) p = 0.006 determined to be attributed to the
dosage to control asthma eucalyptol.
symptoms
Multiple criteria Mean increase of FEV by 0.31 ± 0.36 and 0.2 ± 0.48, AQLQ by Nausea, stomach ache and heartburn were
measurement composed 5.2 ± 8.1 and 2.6 ± 8.1, and sum of assessment of reported in 4 patients that were
of lung function, asthma nocturnal asthma by 3.1 ± 3.8 and 5.22 ± 8.1 in eucalyptol determined to be related to eucalyptol
symptoms and quality of and placebo, respectively. p = .0027 treatment. Not statistically significant.
life.
Decrease in COPD Number of exacerbations (0.9 ± 1.46 vs 0.4 ± 0.82), duration Nausea, diarrhea and heartburn side effects
exacerbation number, of exacerbations (5.7 ± 8.9 vs 4.0 ± 10.9), severity score were only reported in 3 patients.
duration, severity as (1.4 ± 2.2 vs 0.8 ± 1.5) were all significantly decreased (p =
a combined endpoint 0.0024) in Wei-Lachin Test

Dethlefsen, patients in the control and treatment group
were ~42 ± 16 years old and were well matched in
regards to other baseline demographic variables includ-
ing the history of smoking. Many comorbid respiratory
or medical conditions that could affect bronchitis were
exclusion criteria. The mean days from the detection of
acute bronchitis to treatment were 4.0 and 3.9 days in
the control and treatment group, respectively.
Participants assigned to each treatment arm were mea-
sured using the Bronchitis-Sum-Score which summar-
ized symptoms of bronchitis including dyspnea,
sputum, frequency of cough, thoracic pain, auscultation
and lung function – all equally weighted. Both the
eucalyptol and placebo group has a baseline Bronchitis-
Sum-Score of 10. After 4 days of treatment, the euca-
lyptol group had a statistically significant improvement
in symptom alleviation over the placebo group, with
a 0.64 greater decrease in the Bronchitis Sum Score. At
10 days, the severity of symptoms was similar in both
groups, which aligns with normal disease progression,
as acute bronchitis is typically self-limiting and
improves in this time course. When each component
of the Bronchitis-Sum-Score was evaluated, only num-
ber of coughing fits in the eucalyptol group was signifi-
cantly reduced at 4 days and therefore was the main
driver in decreasing the Bronchitis-Sum-Score.
Persistent coughing is the main diagnostic criterion for
acute bronchitis, and thus reduction of coughing fits is
a good indicator for efficacy. Eucalyptol was determined
to be an effective treatment for acute bronchitis with
favorable outcomes on pathophysiology and reduction
of symptoms. This bronchitis treatment is both cost-
effective, accessible and important in reducing inap-
propriate antibiotic prescribing (23).
3.3. Asthma
Asthma is a common chronic disease that affects the air-
ways and makes breathing difficult that could be due to
bronchial hyperresponsiveness, and an underlying inflam-
mation. In a study of severe asthmatics by Juergens et al., 33
participants with a mean age of ~57 years, received an
average daily prednisolone dose of ~11 mg (range 5-24
mg). Additionally, participants received fixed doses of con-
comitant therapy including inhaled corticosteroids (ICS),
inhaled long acting β agonists (LABA), inhaled quaternary
anticholinergics, and theophylline for the studies duration.
They additionally used inhaled short-acting β-agonists
(SABA) as rescue medication on an as-needed basis.
Patients went through a 2-month run-in phase to demon-
strate stability in symptoms and medication dosage. The
study was conducted over 12 weeks with follow-up visits
every 3 weeks, at which oral prednisolone was decreased in
JOURNAL OF ESSENTIAL OIL RESEARCH 5
2.5 mg increments if baseline dose was <20 mg and 5 mg
increments if ≥20 mg as long as asthma symptoms demon-
strated stability. Treatment with eucalyptol allowed
a 2.84 mg greater reduction in daily prednisolone dosage
compared to placebo, demonstrating significant (p = 0.006)
glucocorticoid-sparing effects. Additionally, reductions in
oral glucocorticoids did not result in significant increases in
rescue inhaler use, whereas reductions in placebo groups
did. Patient and clinician global assessments of efficacy
favored eucalyptol compared to placebo. This was the
first study to suggest a clinically relevant anti-
inflammatory activity of eucalyptol in bronchial
asthma (7).
In a recent, larger study with a longer duration of
follow-up conducted by Worth and Dethlefsen, patients
were followed monthly for 6 months. Participants were
required to be controlled for at least 2 weeks prior to
study enrollment and eucalyptol was used as
a concomitant therapy. Enrolled participants had
a mean age of ~53 ± 13 years, has suffered from asthma
for ~15 ± 13 years, and had a mean forced expiratory
volume in 1 s (FEV1) of 2.3 ± 0.8. Patients were well
matched between placebo and treatment group including
baseline use of ICS, LABA, anticholinergic and theophyl-
line, although dose equivalency was not calculated at
baseline. Treatment with eucalyptol showed
a statistically significant improvement in forced expira-
tory volume (FEV1), Asthma Quality of Life
Questionnaire (AQLQ), and nocturnal asthma when
used concomitantly with standard therapy when com-
pared to placebo. Furthermore, eucalyptol treated
patients had significantly increased forced vital capacity
(FVC) and peak flow, as well as improvements in cough,
and dyspnea both at rest and while exercising compared
with placebo. Eucalyptol is thought to help improve
mucociliary dysfunction and to improve patients’ symp-
toms through its anti-inflammatory and bronchodilating
effects. This large randomized trial demonstrated euca-
lyptol improved several dimensions of respiratory func-
tion and quality of life in participants with asthma (30).
3.4. COPD
COPD is a disease of several components in which the
lungs are changed functionally and structurally, resulting
in decreased airflow and oxygen supply to patients.
Smoking is a major risk factor that causes damage to
ciliated epithelium and inflammation to the mucous
membrane. In a 2009 study by Worth, patients were an
average age of about 62 ± 10 years of age, 68% male in the
placebo group, 60% male in the treatment group, about
13 years diagnosed with moderate to severe COPD
(GOLD stages 2 and 3). Patients were well matched, and
6 D. M. GALAN ET AL.
all had been current or previous smokers with an average
of around 31 pack-years history. Patients were followed
for 6 months, with monthly clinic visits, daily patient
diaries, and spirometry testing at baseline, three, and 6
months. Treatment with eucalyptol compared to placebo
showed a statistically significant decrease in frequency
(0.9 ± 1.46 vs 0.4 ± 0.82 exacerbations, respectively),
duration (5.7 ± 8.9 vs 4.0 ± 10.9 days, respectively), and
severity (1.4 ± 2.2 vs 0.8 ± 1.5 exacerbation severity score,
respectively) of COPD exacerbations when used conco-
mitantly with standard therapy (p = 0.0024). Secondary
endpoints such as lung function, dyspnea and quality of
life showed non-significant improvements in forced vital
capacity (FVC) and vital capacity (VC) (p = 0.0627),
dyspnea was significantly improved at rest but not during
exercise, and quality of life measures improved, yet did
not reach statistical significance (p = 0.063). The findings
demonstrate global improvements in several important
parameters related to COPD and shows adding eucalyp-
tol to standard therapy for control of COPD exacerba-
tions is a viable therapeutic strategy (31).
4. Discussion
To date, oral eucalyptol, the major constituent in EOE,
has demonstrated a favorable safety and efficacy profile
in several multi-center, double-blinded, and rando-
mized trials in acute and chronic respiratory conditions
including rhinosinusitis, bronchitis, COPD and asthma.
All trials were conducted in German populations at
outpatient general practice and pneumology clinics.
Eucalyptol was administered ~20 min prior to a meal in
order to alleviate potential gastric-related adverse effects
and help to improve blinding as the ability to taste euca-
lyptol upon eructation was potentially reduced. The dose
of eucalyptol was invariably 200 mg PO three times daily
across trials; however, study duration varied by indica-
tion. Thrice daily administration may introduce signifi-
cant pill burden for some patients. In chronic respiratory
illnesses eucalyptol has been given for up to 6 months
without apparent deleterious effects or tolerance/loss of
efficacy. This is a longer duration than many short-term
efficacy trials; however, due to chronicity of asthma or
COPD, it may be desirable to conduct longer-term safety
studies. Generally, studies used guideline-based diagnos-
tic criteria and validated rating scales or spirometry to
measure outcomes. Most studies allowed concomitant
use of other pharmacologic agents to avoid ethical or
safety concerns and measured eucalyptol’s effect as
a therapy adjunct, with the exception of acute bronchitis,
which is a self-limiting illness that often doesn’t require
pharmacologic intervention. To the ability of discern-
ment available in study manuscripts, it appears the
concurrent therapies did not significantly influence or
bias study results.
While the focus of this review was eucalyptol in
isolation, there is a proprietary terpenoid blend available
that includes eucalyptol, d-limonene, and alpha-pinene
(GeloMyrtol™) that has also demonstrated favorable
efficacy and safety profiles in randomized trials for the
treatment of respiratory disorders including acute and
chronic rhinosinusitis, chronic bronchitis, and COPD
(35). While direct comparison is not possible between
data sets due to heterogeneity in populations or out-
comes studied, it shows that monoterpenoid combina-
tions can also be useful in respiratory conditions and
suggests there may yet to be even more efficacious
therapies available for respiratory conditions using
essential oils or their constituents.
To this end, from the perspective of evidence-based
medicine, it is currently unclear if EOE could be used
similarly due to the presence of several other consti-
tuents, some of which may modulate efficacy and/or
toxicity. However, from the folkloric perspective, full-
spectrum aromatics from eucalyptus plant materials
have always been used. A dose in drops of EOE may
be approximated by using the estimated density of
eucalyptol: The density of eucalyptol is around
0.9267 g/mL at 20°C. Thus, ~0.2 ml of eucalyptus oil
would equal about ~200 mg. Assuming 20 drops
per ml, then 4 drops would be around 200 mg (36).
Therefore, the oral dose could equate to approxi-
mately 4 drops of oral eucalyptol three times
per day if replicating dose of 200 mg orally three
times daily. The use of undiluted eucalyptol or EOE
may lead to irritation of the gastric lining and dose
may be better tolerated if diluted. Due to complexities
in compounding oral treatments using essential oils
and the availability of eucalyptol in 100 mg standar-
dized gel capsules (Cold Capsules™, Soledum™) it may
be easier and safer for clinicians to recommend avail-
able products.
It is somewhat surprising, given the widespread use of
inhaled eucalyptus aromatics in folkloric and traditional
medicine systems, that there has never been
a randomized trial of inhaled eucalyptol for the treatment
of a respiratory condition. Given that most respiratory
medicines for asthma and COPD are delivered via the
inhalation route to avoid systemic side effects and boost
drug concentrations in targeted respiratory tissues, this
seems an important line of inquiry to pursue further.
There are numerous home diffusion devices available
and may be interesting to understand if low concentra-
tions of EOE in ambient atmospheres reduce respiratory
symptoms such as nocturnal awakenings due to asthma
when diffused nightly in a bedroom. Alternatively, there

are other devices commercially available or simply con-
structed that can deliver aromatics, such as essential oils,
directly to lung tissue and may be suitable for COPD
exacerbations, asthma attacks, or infections (2).
There are limitations of this review as well as the
studies analyzed that deserve mention. We performed
a limited search of databases and included only English
articles. Given that the majority of eucalyptol research for
respiratory conditions is conducted in Germany and that
many traditional or folkloric medicine systems are not
based upon English-speaking cultures, there is
a possibility we did not capture the entirety of available
data. One of the studies had a small sample size and
despite showing decreases in prednisolone dosage, most
participants remained on corticosteroids at the study’s
end and were not allowed to change maintenance medi-
cations, which may lead one to question the clinical
significance of eucalyptol in severe asthmatics (7). Other
studies in asthma and COPD had matched demographic
samples regarding the incidence of medication use, but
did not calculate inhaled steroid dose equivalency,
attempt to investigate if doses between groups were clo-
sely matched, or report changes in rescue inhaler utiliza-
tion, which could have introduced bias (30,31).
5. Conclusion
Eucalyptol has displayed efficacy with good tolerability
in a range of acute and chronic respiratory conditions
and may be a useful ally to employ in the treatment of
respiratory illness along with standard therapies.
Disclosure statement
None of the authors has any pertinent financial conflicts of
interest or disclosures with the exception of Dr. Nicholas
Berry, who owns an essential oils business called ‘Essential
Oil Wizardry’.
ORCID
Benjamin J. Malcolm http://orcid.org/0000-0002-9293-
9036
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